title: Resistance to ceftazidime in Escherichia coli associated with AcrR, MarR and PBP3 mutations and overexpression of sdiA.
abstract: The mechanisms responsible for the increase in ceftazidime MIC in two Escherichia coli in vitro selected mutants, Caz/20-1 and Caz/20-2, were studied. OmpF loss and overexpression of acrB, acrD and acrF that were associated with acrR and marR mutations and sdiA overexpression, together with mutations A233T and I332V in FtSI (PBP3) resulted in ceftazidime resistance in Caz/20-2, multiplying by 128-fold the ceftazidime MIC in the parental clinical isolate PS/20. Absence of detectable β-lactamase hydrolytic activity in the crude extract of Caz/20-2 was observed, and coincided with Q191K and P209S mutations in AmpC and a nucleotide substitution at -28 in the ampC promoter, whereas β-lactamase hydrolytic activity in crude extracts of PS/20 and Caz/20-1 strains was detected. Nevertheless, a fourfold increase in ceftazidime MIC in Caz/20-1 compared with that in PS/20 was due to the increased transcript level of acrB derived from acrR mutation. The two Caz mutants and PS/20 showed the same mutations in AmpG and ParE.
authors.affiliation: Unidad de Epidemiología y Medicina Preventiva, Instituto Universitario de Sanidad Animal (IUSA), Universidad de Las Palmas de Gran Canaria, Arucas, Spain.|Microbiología, Departamento de Ciencias Clínicas, Facultad de Ciencias de la Salud, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
authors.forename: María M
authors.initials: MM
authors.lastname: Tavío
authors.affiliation: Microbiología, Departamento de Ciencias Clínicas, Facultad de Ciencias de la Salud, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
authors.forename: Virginia D
authors.initials: VD
authors.lastname: Aquili
authors.affiliation: Departamento de Microbiología, IDIBAPS, Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
authors.affiliation: Unidad de Epidemiología y Medicina Preventiva, Instituto Universitario de Sanidad Animal (IUSA), Universidad de Las Palmas de Gran Canaria, Arucas, Spain.
authors.forename: José B
authors.initials: JB
authors.lastname: Poveda
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000096:biosynthesis* / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012641:Selection, Genetic; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D002442:Ceftazidime